Antimicrobial polyurethane foam and process to make the same

ABSTRACT

An antimicrobial polyurethane foam that is formed from: a multi-functional isocyanate component; an aqueous polyol component reactive with the multi-functional isocyanate component; an antimicrobial metallic compound; and a complexing agent. The complexing agent is used to form a stable blend of the antimicrobial metallic compound with the polyol component. Exemplary complexing agents include amine compounds, ammonium-containing compounds, and ammonia as well as combinations of these compounds. The antimicrobial metallic compound can be a silver, zinc, or copper compound. Desirably, the antimicrobial metallic compound is silver saccharinate. A process of making the antimicrobial polyurethane foam and stable blends used in the manufacture of the antimicrobial polyurethane foam are also disclosed.

This application claims the benefit of priority from U.S. ProvisionalApplication No. 61/497,840 filed on Jun. 16, 2011.

FIELD OF THE INVENTION

The present invention relates generally to foamed plastic materials andmore particularly to foamed polyurethanes having antimicrobialproperties.

BACKGROUND

The versatility and economics of flexible cellular foamed polyurethanematerials (referred to as “polyurethane foams”) have resulted in theiradaptation for variety of uses including furniture cushioning, carpetunderlayment, and cosmetic and medical applications such as absorbentwound dressings. In such application, it is desirable that dressingsremain in place for several days to absorb the wound exudate and tominimize dressing changes to reduce the risk of trauma to the healingwound. It is also desirable that such foam wound dressings not supportmicro-organism growth but aid in lowering the bio-burden. Thus,antimicrobial properties are very much desired in the foam material usedin wound care applications.

There are several antimicrobial foam dressings in the market. Examplesinclude PolyMem®, an antimicrobial foam dressing and Bio-Patch®, anantimicrobial site dressing. Silver is the active in the PolyMem®product and an organic compound is the active in the Bio-Patch® product.Considering the fact silver is a broad spectrum antimicrobial and hasbeen widely incorporated in a variety of wound care products,introducing silver into foam products has proved somewhat challenging.The difficulty of incorporating silver chemistries in foam productsstems from its susceptibility to chemical reduction to metallic silverin the presence of polyurethane precursors. Post reduction, the presenceof metallic silver imparts black or brown color to the foam such is thecase with PolyMem® foam dressing.

In advancing the art, PCT International Publication WO 2004/007595 A1 byLendell et al. for “Antimicrobial Polyurethane Foam” describes flexiblepolyurethane foam (i.e., foamed polyurethane) that incorporates asilver-based antimicrobial agent in the form of silver sodium hydrogenzirconium phosphate available as Antimicrobial AlphaSan® from MillikenChemical of Spartanburg, S.C. This material may be mixed in with apolyisocyanate (i.e., multi-functional isocyanate) component or a polyolcomponent (or both) prior to reaction.

One disadvantage with silver sodium hydrogen zirconium phosphate is thatsilver is not readily available for antimicrobial action. A large amountof the active agent is required to ensure a minimum efficacy thresholdand to sustain long duration activity thus adding to the cost.

Accordingly, there is a need for improved antimicrobial polyurethanefoam products. For example, there is a need for flexible cellularpolyurethane foam products and flexible cellular hydrophilicpolyurethane foam products that resist discoloration. This need extendsto antimicrobial polyurethane foam products incorporating metal-basedantimicrobial compositions. There is also a need for antimicrobialpolyurethane foam products having a uniform distribution of metal-basedantimicrobial compositions that resist discoloration.

SUMMARY

In response to the difficulties and problems discussed herein, thepresent inventors have discovered that certain antimicrobialcompositions that comprise weakly soluble silver salt or a mixturethereof and silver nanoparticles, when incorporated into foam productsproduced by the methods of the PCT International Publication WO2004/007595 A1, provide foam products that are antimicrobial and resistdiscoloration in ambient light conditions and during sterilizationprocesses.

The present invention thus provides antimicrobial compositions includingan antimicrobial metallic compound in the form of a weakly soluble metalsalt or a mixture a weakly soluble metal salt and metal nanoparticlesfor producing discoloration-resistant antimicrobial polyurethane foam.For example, the antimicrobial compositions include an antimicrobialmetallic compound in the form of a weakly soluble silver salt or amixture a weakly soluble silver salt and silver nanoparticles forproducing discoloration-resistant antimicrobial polyurethane foam.

The present invention also provides methods of generating theantimicrobial compositions for producing antimicrobial polyurethanefoams, the methods of making the antimicrobial polyurethane foamsincorporating such antimicrobial compositions, and the antimicrobialfoams produced.

Generally speaking, the antimicrobial compositions include a weaklysoluble metal salt (e.g., silver salt) and metal nanoparticles (e.g.,silver nanoparticles) and a solvent. Desirably, the solvent is water ora mixture where more than 50% by weight is water. Alternatively and/oradditionally, the antimicrobial compositions may further include asoluble ammonia complex of the weakly soluble metal salt (e.g., silversalt). Antimicrobial compositions also further include a soluble ammoniacomplex of the weakly soluble metal salt (e.g., silver salt), metalnanoparticles (e.g., silver nanoparticles) and a solvent.

According to the invention, the complexing agent is used to solubilizethe antimicrobial metallic compound in the solvent used. Exemplarycomplexing agents include amine compounds, ammonium-containing compoundsand ammonia, and ammonium hydroxide as well as combinations of thesecompounds, though the preferred complexing agent is ammonia.

The antimicrobial metallic compound can be a silver, zinc or coppercompound. For example, the antimicrobial metallic compound may becopper, zinc, or silver diazepine complexes, polymeric silver compounds,polymeric copper compounds, polymeric zinc compounds, copper compoundsof saccharin, zinc compounds of saccharin, and silver compounds ofsaccharin. Desirably, the antimicrobial metallic compound is silversaccharinate.

The aqueous polyol component may be any conventional polyol used to formpolyurethanes. Exemplary aqueous polyols include polyhydroxy-containingpolyesters, polyoxyalkylene polyether polyols, polyhydroxy-terminatedpolyurethane polymers, polyhydroxy-containing phosphorus compounds, andalkylene oxide adducts of polyhydric polythioesters, polyacetals,aliphatic polyols and thiols, and mixtures thereof. Desirably, theaqueous polyol component is a polyether polyol.

The multi-functional isocyanate component may be any conventionalmulti-functional isocyanate used to form polyurethanes. Exemplarymulti-functional isocyanates include toluene diisocyanate, monomericmethylene diisocyanate, polymeric methylene diisocyanate, andcombinations thereof.

The composition may further include a chain extender. The chain extendermay be an aromatic or aliphatic compound capable of reacting with atleast two isocyanate terminated polymer units to form a polymer chain.Exemplary chain extenders may be aromatic or aliphatic compounds whichare terminated with more than one hydroxyl or amine groups.

The present invention encompasses discoloration-resistant antimicrobialpolyurethane foam that is the reaction product of: a multi-functionalisocyanate component; an aqueous polyol component reactive with themulti-functional isocyanate component; an antimicrobial metalliccompound complexed with a complexing agent and, optionally, silvernanoparticles.

The present invention also encompasses a process for producingdiscoloration-resistant antimicrobial polyurethane foam. The processincludes the steps of: providing an aqueous polyol component; adding anantimicrobial metallic compound (e.g., one or more weakly soluble metalsalts) and a complexing agent to form a complex that is soluble in theaqueous polyol component (alternatively and/or additionally, metalnanoparticles may be included with the soluble complex); solubilizingthe antimicrobial metallic compound complex in the aqueous polyolcomponent to form a stable blend; mixing a multi-functional isocyanatecomponent with the stable blend; and reacting the multi-functionalisocyanate component with the aqueous polyol to form a polyurethane foamincorporating the antimicrobial metallic compound. A key distinguishingaspect of the process of making the antimicrobial polyurethane foam ofthe present invention is that despite being added as a complex with thecomplexing agent and the antimicrobial metallic compound, it is presentas substantially only the antimicrobial metallic compound in thefinished foam (and/or as antimicrobial metal nanoparticles, if they wereadded).

In one embodiment of the invention, the isocyanate prepolymer (preparedby reacting multi-functional isocyanates with low molecular weightdiols, triols, dial kylene glycols, trialkylene glycols orpolyoxyalkylene glycols of molecular weights up to 8000) is mixed withan aqueous solution comprising a thickener (to impart increasedhydrophilicity) and a surfactant (to adjust the foam characteristics),and an antimicrobial metallic compound (e.g., silver saccharinate)complexed with a complexing agent such as, for example, ammonia (andoptionally, metal nanoparticles complexed with a complexing agent) toproduce antimicrobial foam.

Preferred quantities of the thickener and the surfactant are less thanabout five percent (5%) by weight of the aqueous solution. Desirably,the pH of the aqueous solution is in the range of 8 to 11 with mostdesirably the pH being around 10. The preferred amount of metalantimicrobial particles (e.g., silver present as nanoparticles) is fromabout 50 to about 10,000 parts per million (ppm) by weight based on theweight of the dry foam with most desirably the amount being betweenabout 50 to about 2000 ppm. Desirably, the amount of antimicrobialmetallic compound (e.g., weakly soluble silver salt) in the finishedfoam is less than five percent (5%) by weight based on the weight of thedry foam with most desirably the amount being less than one percent (1%)by weight based on the weight of the dry foam. Note by “dry foam” it ismeant the finished foam which is substantially dry—but may actuallycontain a small amount of residual moisture, which usually is less than5% by weight of the finished foam. For example, the amount ofantimicrobial metallic compound (e.g., weakly soluble silver salt) inthe finished foam may be from about 0% to about less than five percent(5%) by weight based on the weight of the dry foam. However, whenantimicrobial metallic compound is absent in the foam (i.e. 0%), itshould desirably still contain metal present as elemental nanoparticleshaving antimicrobial properties. Thus, the antimicrobial foam of thepresent invention as contemplated is never devoid of antimicrobialmetal.

The anions associated with the metallic compound are those that areconsidered biocompatible in the ranges used and considered GRAS(generally regarded as safe) by the U.S. FDA. The metal nanoparticlessuch as silver nanoparticles used in the antimicrobial polyurethane foamare generally smaller than 100 nm; most preferably their averagediameter in the range of 5 to 50 nm. The preferred shape of the silvernanoparticles used in the foam of the present invention is spheroidal.However, silver nanoparticles of shapes other than spheroidal areencompassed by the present invention.

According to an aspect of the present invention, there is provided anantimicrobial polyurethane foam including silver nanoparticles (e.g.,average diameter between 5 and 50 nm) that imparts a permanent color ofthe visible portion of the UV-VIS spectrum without the use of a colorant(such as, for example, dyes or pigments) and that the color is notinherent to the reactive components used to produce the foam or isattributed to other additives or ingredients present in the foam.Optionally, the polyurethane foam having color may be made without thepresence of an antimicrobial metallic compound (i.e., the foam mayincorporate only metal nanoparticles such as silver nanoparticles as themetal-based antimicrobial material). Such foam may be less effective asantimicrobial material but may possess sufficient activity to bebacteriostatic and may find applications as filler material forcushions, pillows, and as an odor absorbing matrix.

Yet another aspect of the present invention provides a method ofimparting to the antimicrobial polyurethane a permanent color of thevisible portion of the UV-VIS spectrum without the use of a colorant(known as dye or pigment) and that the color is not inherent to thereactive components used to produce the foam or is attributed to otheradditives in the foam, by the use of the nanoparticles of silver andgenerally by the use of nanoparticles of heavy metals.

In yet another aspect, the present invention provides an antimicrobialpolyurethane foam that is hydrophilic, absorbent, contains plurality ofopen cells, is light weight, is reasonably resistant to discoloration byambient light, and is resistant to the discoloration induced bysterilization processes such as ethylene oxide (ETO) and electron beam(E-beam) irradiation.

Yet another aspect of the present invention is to provide polyurethanefoam that sustains antimicrobial activity against gram positivebacteria, gram negative bacteria, and fungi for more than 7 days byreleasing a therapeutically effective amount of metal ions such as ionicsilver.

Yet another aspect of the present invention is to provide a suitablemethod of incorporating antimicrobial metallic compounds to effect moreuniform distribution of the said compound within the foam matrix duringthe process of making antimicrobial polyurethane foam.

Other objects, advantages, and applications of the present disclosurewill be made clear by the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a black and white photograph illustrating samples of exemplaryantimicrobial polyurethane foam containing silver nanoparticles aftersterilization by electron beam irradiation and ethylene oxide techniquesand a control sample.

FIG. 2 is a black and white photograph illustrating samples of exemplaryantimicrobial polyurethane foam containing silver saccharinate aftersterilization by electron beam irradiation and ethylene oxide techniquesand a control sample.

FIG. 3 is a black and white photograph illustrating samples of exemplaryantimicrobial polyurethane foam containing both silver nanoparticles andsilver saccharinate after sterilization by electron beam irradiation andethylene oxide techniques and a control sample.

DETAILED DESCRIPTION

Reference will now be made in detail to one or more embodiments of theinvention. It should be understood that features illustrated ordescribed as part of one embodiment may be used with another embodimentto yield still a further embodiment. It is intended that the claimsinclude these and other modifications and variations as coming withinthe scope and spirit of the disclosure.

As used herein, the term “complexing agent” refers to a substance thatforms a complex compound with another material in solution. Exemplarycomplexing agents provide ions or molecules (also called ligands) thatbind to a central metal atom. Ligands may be generated from amines,ammonia containing compounds, ammonia, phosphines, CO, N₂ and alkenes.Though, ligands with ammonia are preferred.

As used herein, the term “discoloration” refers to changes in colorlevels measured and recorded CIELAB coordinates using a Hunter Lab ColorDifference Meter, Model D25 Optical Sensor and manufactured by HunterAssociates Laboratory, Reston, Va. CIELAB coordinates are a systemagreed upon in 1976 within the “Commission Internationale deI'Eclairage” or CIE. The coordinates are designated L*, a*, b*. Thesystem uses a three axis opponent color scale assuming color isperceived in white to black (L*) or “lightness”, green to red (a*), andyellow to blue (b*) sensations. L* varies from 100 for a perfect whiteto zero for a perfect black. a* measures redness when plus (i.e.,positive), grey when zero, and greenness when minus (i.e., negative). b*measures yellowness when plus (i.e., positive), grey when zero, andblueness when minus (i.e., negative).

As used herein, the term “discoloration-resistant” refers to the abilityof a material to avoid meaningful changes in CIELAB color levels incomparison to similar conventional materials under essentially identicalconditions such as, for example, exposure to a conventional ethyleneoxide sterilization cycle or electron beam irradiation sterilizationcycle. For example, an antimicrobial polyurethane foam containing fromabout one percent (1%) by weight silver saccharinate powder based on thedry weight of the foam may avoid meaningful changes in CIELAB colorlevels in comparison to an antimicrobial polyurethane foam containingabout one percent (1%) by weight Antimicrobial AlphaSan® based on thedry weight of the foam after exposure to a conventional ethylene oxidesterilization cycle or electron beam irradiation sterilization cycle.

As used herein, the term “resistant to discoloration by light” refers tothe ability of a material to avoid meaningful changes in CIELAB colorlevels in comparison to similar conventional materials under essentiallyidentical conditions such as exposure to light of a specified wavelengthor to ambient light for a specified length of time. For example, anantimicrobial polyurethane foam containing from about one percent (1%)by weight silver saccharinate powder based on the dry weight of the foammay avoid meaningful changes in CIELAB color levels in comparison to anantimicrobial polyurethane foam containing about one percent (1%) byweight Antimicrobial AlphaSan® based on the dry weight of the foam afterexposure to ambient light for two (2) hours.

As used herein, the term “stable blend” refers to a mixture including asolvent or mixture of solvents, polyol, and actives (antimicrobialmetallic compound as complex with complexing agent and elementalnanoparticles) that remains homogeneous (as single phase) forapproximately at least 24 hours at normal room temperature(approximately 25° C.). The mixture may further include one or morethickeners, surfactants and combinations thereof.

As used herein, the term “foam” refers to foamed plastic materials (alsosometimes called “cellular plastics”, “cellular polymers”, “plasticfoams” or “expanded plastics”) and more specifically refers to plasticmaterials in which the apparent density is decreased by the presence ofnumerous cells disposed throughout its mass. Such materials aretwo-phase gas-solid systems in which the solid is continuous andcomposed of a polymer. Desirably, the cells are interconnected in such amanner that gas or liquid can pass from one to another—such materialsare referred to as open cell and/or reticulated materials. Foams may berigid or flexible. One exemplary standard test that may be used tocharacterize the flexibility of foams is ASTM D1566-10e1 “StandardTerminology Relating to Rubber”.

As used herein, the term, “antimicrobial” refers to a substance thatkills or inhibits the growth of microorganisms. Exemplary antimicrobialmaterials include metal ions that are eluted from metal particles. Suchmaterials may exhibit antimicrobial properties when used at sufficientlyhigh concentrations and/or with agents that enhance elution of ionsand/or inhibit the deactivation of the ions.

The present invention provides a composition for producing antimicrobialfoamed plastic materials. Generally speaking, these antimicrobial foamedplastic materials are made from polyurethane that incorporate one ormore antimicrobial metallic compounds in the form of a weakly solublemetal salt(s) or a mixture of a weakly soluble metal salt(s) and metalnanoparticles. Desirably, these materials producediscoloration-resistant antimicrobial polyurethane foam.

Generally speaking, the composition includes a multi-functionalisocyanate component; an aqueous polyol component reactive with themulti-functional isocyanate component; an antimicrobial metalliccompound; and a complexing agent.

According to the invention, the complexing agent is used to solubilizethe antimicrobial metallic compound in the solvent used for thecomposition. That is, the complexing agent forms a complex with theantimicrobial metallic compound such that the complex is soluble in thesolvent used for the composition. Exemplary complexing agents includeamine compounds, ammonium-containing compounds (including but notlimited to ammonium hydroxide), and ammonia as well as combinations ofthese compounds. It is contemplated that phosphines, CO, N₂, and alkenesmay also be used. Though, the preference is for ligands with ammonia orammonium containing compounds.

The antimicrobial metallic compound can be a silver, zinc, or coppercompound such as, for example, one or more weakly soluble metal salts.For ease of reference, silver will be used herein, but it is to beunderstood that any one of the three metals is intended. Theantimicrobial metallic compound may be silver diazepine complexes,polymeric silver compounds, and silver compounds of saccharin.Desirably, the antimicrobial metallic compound is silver saccharinate.

By weakly soluble metallic salt or compound, it is meant those saltsthat generally have solubility in water at 25° C. of 10 grams per literor less. However, salts having higher aqueous solubility may also beused in the practice of the present invention.

In addition to the antimicrobial metallic compound that interacts withthe complexing agent to form a complex that is soluble in the solventfor the composition, metal nanoparticles (e.g., silver nanoparticles)may optionally be added to the composition as noted above. A thin metaloxide coating typically forms on the surface of such metal nanoparticlessuch that the oxide layer is capable of forming a water soluble complexwith the complexing agent. While the inventors should not be held to aparticular theory of operation, these water soluble complexes (i.e.,complexes incorporating the antimicrobial metallic compound and,optionally, the metal nanoparticles) allow for excellent dispersion ofthe antimicrobial metallic compound and metal nanoparticles throughoutthe foamed plastic when properly mixed with the foam ingredients.

In one embodiment of the invention, the antimicrobial metallic compoundand the elemental nanoparticles may not be derived from the samemetallic element. For example, the antimicrobial metallic compound maybe a silver based salt or a compound and the metallic nanoparticles maybe of copper and/or zinc. In an alternate embodiment, the metalliccompound or salt may be copper and/or zinc based whereas the elementalnanoparticles may be made of silver. Both combinations are encompassedby the present invention.

The aqueous polyol component may be any conventional polyol used to formpolyurethanes. The polyol component is desirably composed of one or morepolyol compounds. If a hydrophilic polyurethane foam product is desired,the aqueous solution component is desirably composed of water and one ormore polyol compounds, such that at least 50% of the hydroxyl (—OH)functional groups of the polyol component are secondary hydroxyl groups.

Exemplary aqueous polyols include polyhydroxy-containing polyesters,polyoxyalkylene polyether polyols, polyhydroxy-terminated polyurethanepolymers, polyhydroxy-containing phosphorus compounds, and alkyleneoxide adducts of polyhydric polythioesters, polyacetals, aliphaticpolyols and thiols, and mixtures thereof. Desirably, the aqueous polyolcomponent is a polyether polyol.

The polyether polyol composition may desirably contain a predominantamount of secondary hydroxyl groups, with a composition containing allsecondary hydroxyl groups being preferred. By a predominant amount ofsecondary hydroxyl group containing polyether polyol composition, it ismeant that at least fifty weight percent of the hydroxyl groups shouldbe secondary hydroxyl groups such as those derived from propylene oxide.

Methods of making polyether polyols are well known and include thosepolyethers prepared from the base catalyzed addition of an alkyleneoxide such as, but not limited to ethylene oxide, propylene oxide, orbutylenes oxide, preferably ethylene oxide, to an initiator moleculecontaining, on the average, two or more active hydrogens. Thepolyalkylene polyether polyols are well known in the art and may beprepared by any known process, Examples of initiator molecules include,without limitation, diethylene glycol, ethylene glycol, dipropyleneglycol, propylene glycol, trimethylene glycol, 51,2-butanediol,1,3-butanediol, 1,4-butanediol, 1,4-pentanediol, 1,5-pentanediol,1,6-hexanediol, 1,7-heptanediol, glycerine, 1,1,1-trimethyolpropane,1,1,1 trimethylolethane, 1,2,6-hexantriol, or triethylolpropane.

The multi-functional isocyanate component may be any conventionalmulti-functional isocyanate used to form polyurethanes. Exemplarymulti-functional isocyanates include toluene diisocyanate, monomericmethylene diisocyanate, polymeric methylene diisocyanate, andcombinations thereof. These multi-functional isocyanates are generallywell known in the art, and include, without limitation, 4,4′-, 2,4′-,and 2 2′-diphenylmethane diisocyanate, variouspolyphenylenepolymethylene multi-functional isocyanates (polymeric MDI),and mixtures of some or all of these compounds.

The multi-functional isocyanate component may also include one or moreother aliphatic, cycloaliphatic, arylaliphatic, and/or aromaticmulti-functional isocyanates. The multifunctional isocyanate componentshould desirably contain at least 80% by weight methylene diisocyanate(MDI) or polymeric methylene diisocyanate (MDI).

Modified multivalent isocyanates which are products obtained by thepartial chemical reaction of organic diisocyanates and/ormulti-functional isocyanates may be used. Examples include, withoutlimitation, diisocyanates and/or multi-functional isocyanates containingester groups, urea groups, biuret groups, allophanate groups,carbodiimide groups, isocyanurate groups, and/or urethane groups.

The composition may further include a chain extender. The chain extendermay be an aromatic or aliphatic compound capable of reacting with atleast two isocyanate terminated polymers units to form a polymer chain.Exemplary chain extenders may be aromatic or aliphatic compounds whichare terminated with more than one hydroxyl or amine groups. Theseinclude compounds having at least two functional groups bearing activehydrogen atoms such as, but not limited to water, hydrazine, primary andsecondary diamines, amino alcohols, amino acids, hydroxy acids, glycols,or mixtures thereof. An exemplary group of chain-extenders includes,without limitation, water, ethylene glycol, 1,4-butanediol, and primaryand secondary diamines which react more readily with the prepolymer thandoes water such as, but not limited to phenylene diamine,1,4-cyclohexane-bis-(methylamine), ethylenediamine, diethylenetriamine,N-(2-hydroxylpropyl)ethylenediamine,N,N′-di(2-hydroxypropyl)ethylenediamine, piperazine, and2-methylpiperazine.

The foamed polyurethane materials are generally prepared by the reactionof a polyoxyalkylene polyether polyol with an organic multi-functionalisocyanate in the presence of a blowing agent and optionally in thepresence of additional polyhydroxyl-containing components,chain-extending agents, catalysts, surfactants, stabilizers, dyes,fillers, and pigments. Generally speaking, the reaction conditions toproduce foamed polyurethane materials would be readily determined by oneof ordinary skill in the art.

Any suitable catalysts or surfactants may be used, along with suitableprocesses for the preparation of cellular polyurethane foams asdisclosed in U.S. Pat. No. Re. 24,514, the entire content of which isincorporated herein by reference, together with suitable machinery to beused in conjunction therewith. When water is added to generate carbondioxide as blowing agent, corresponding quantities of excess isocyanateto react with water may be used. Such processes are generally referredto as conventional “pre-polymer processes” or “pre-polymer techniques”.

It is contemplated that one may proceed with the preparation of thefoamed polyurethane materials by a pre-polymer technique wherein anexcess of organic multi-functional isocyanate is reacted in a first stepwith the polyol to prepare a pre-polymer having free isocyanate groupswhich is then reacted in a second step with water and/or additionalpolyol to prepare a foam. Alternatively, the components may be reactedin a single working step commonly known as the “one-shot” technique ofpreparing foamed polyurethane materials.

The present invention encompasses antimicrobial polyurethane foam thatis the reaction product of: a multi-functional isocyanate component; anaqueous polyol component reactive with the multi-functional isocyanatecomponent; an antimicrobial metallic compound that may desirably beresistant to discoloration by light; and a complexing agent. Thematerials used to prepare the antimicrobial polyurethane foam are asgenerally described above. The antimicrobial polyurethane foam mayfurther include antimicrobial metal nanoparticles or, in some versions,the antimicrobial metal nanoparticles may be used instead of theantimicrobial metallic compound.

Desirably, the amount of antimicrobial metallic compound (e.g., weaklysoluble silver salt) in the finished foam is less than five percent (5%)by weight based on the weight of the dry foam with the most desirableamount being less than one percent (1%) by weight based on the weight ofthe dry foam. Note by “dry foam” it is meant the finished foam which isat least substantially dry—but may actually contain a small amount ofresidual moisture, which usually is less than 5% by weight of thefinished foam. For example, the amount of antimicrobial metalliccompound (e.g., weakly soluble silver salt) in the finished foam may befrom about 0% to about less than five percent (5%) by weight based onthe weight of the dry foam. However, when antimicrobial metalliccompound is absent in the foam (i.e. 0%), it may still contain metalpresent as elemental nanoparticles having antimicrobial properties.Thus, the antimicrobial foam of the present invention as contemplated isnever devoid of antimicrobial metal.

The anions associated with the metallic compound are those that areconsidered biocompatible in the ranges used and considered GRAS(Generally Regarded As Safe) by the U.S. Food and Drug Administration.If antimicrobial metal nanoparticles are incorporated in theantimicrobial polyurethane foam, the metal nanoparticles such as, forexample, silver nanoparticles are generally smaller than 100 nm; mostpreferably their average diameter in the range of 5 to 50 nm. Thepreferred shape of the silver nanoparticles used in the foam of thepresent invention is spheroidal. However, silver nanoparticles of shapesother than spheroidal are encompassed by the present invention. Thepreferred amount of metal antimicrobial particles (e.g., silver presentas nanoparticles) is from about 50 to about 10,000 parts per million(ppm) by weight based on the weight of the dry foam with most desirableamount being between about 50 to about 2000 ppm.

The present invention also encompasses a process for producingantimicrobial polyurethane foam. Desirably, the process producesantimicrobial polyurethane foam that is discoloration resistant. Theprocess includes the steps of: providing an aqueous polyol component;adding an antimicrobial metallic compound (e.g., one or more weaklysoluble metal salts) and a complexing agent to form a complex that issoluble in the aqueous polyol component (alternatively and/oradditionally, metal nanoparticles may be included in the solublecomplex); solubilizing the antimicrobial metallic compound complex inthe aqueous polyol component to form a stable blend; mixing amulti-functional isocyanate component with the stable blend; andreacting the multi-functional isocyanate component with the aqueouspolyol to form a polyurethane foam incorporating the antimicrobialmetallic compound.

In an aspect of the invention, the process further includes the step ofallowing the complexing agent to dissipate such that the antimicrobialmetallic compound is present as substantially only the antimicrobialmetallic compound in the finished foam (and/or as antimicrobial metalnanoparticles, if they were added).

According to an aspect of the invention, the complexing agent may be acatalyst for the reaction of the multi-functional isocyanate componentwith the aqueous polyol. Desirably, the complexing agent will be ammoniaor an ammonium-containing compound. Furthermore, the process may includethe step of adding a chain extender.

In one embodiment of the invention, the isocyanate prepolymer (preparedby reacting polyisocyanates with low molecular weight diols, triols,dialkylene glycols, trialkylene glycols or polyoxyalkylene glycols ofmolecular weights up to 8000) is mixed with an aqueous solutionincluding a thickener (which may be used to impart increasedhydrophilicity) and a surfactant (which may be used to adjust the foamcharacteristics), and an antimicrobial metallic compound (e.g., silversaccharinate) complexed with a complexing agent such as, for example,ammonia (and optionally, metal nanoparticles complexed with a complexingagent) to produce antimicrobial foam.

Preferred quantities of the thickener and the surfactant are less thanabout five percent (5%) by weight of the aqueous solution. Desirably,the pH of the aqueous solution is in the range of 8 to 11 with mostdesirably the pH being around 10.

Another aspect of the present invention addresses a method for producinga stable blend used in the manufacture of antimicrobial polyurethanematerials. The method includes the steps of: providing an aqueous polyolcomponent; adding an antimicrobial material selected from antimicrobialmetallic compounds, antimicrobial metal nanoparticles and mixturesthereof, and a complexing agent to form a complex that is soluble in theaqueous polyol; and solubilizing the antimicrobial metallic compoundcomplex in the aqueous polyol component to form a stable blend.

According to the method, the complexing agent may be amine compounds,ammonium-containing compounds and ammonia, and combinations thereof; andthe complexing agent may further serve as a catalyst for the reaction ofthe aqueous polyol component and a multi-functional isocyanatecomponent.

According to an aspect of the present invention, there is provided anantimicrobial polyurethane foam including silver nanoparticles (e.g.,average diameter between 5 and 50 nm) that imparts a permanent color ofthe visible portion of the UV-VIS spectrum without the use of a colorant(such as, for example, dyes or pigments) and that the color is notinherent to the reactive components used to produce the foam or isattributed to other additives or ingredients present in the foam.Optionally, the polyurethane foam having color may be made without thepresence of an antimicrobial metallic compound (i.e., the foam mayincorporate only metal nanoparticles such as silver nanoparticles as themetal-based antimicrobial material). Such foam may be less effective asantimicrobial material but may possess sufficient activity to bebacteriostatic and may find applications as filler material forcushions, pillows, and as an odor absorbing matrix.

Yet another aspect of the present invention provides a method ofimparting to the antimicrobial polyurethane a permanent color of thevisible portion of the UV-VIS spectrum without the use of a colorant(known as dye or pigment) and that the color is not inherent to thereactive components used to produce the foam or is attributed to otheradditives in the foam, by the use of the nanoparticles of silver andgenerally by the use of nanoparticles of heavy metals.

In yet another aspect, the present invention provides an antimicrobialpolyurethane foam that is hydrophilic, absorbent, contains plurality ofopen cells, is light weight, is reasonably resistant to discoloration byambient light, and is resistant to the discoloration induced bysterilization processes such as ethylene oxide (ETO) and electron beam(E-beam) irradiation.

Yet another aspect of the present invention is to provide polyurethanefoam that sustains antimicrobial activity against gram positivebacteria, gram negative bacteria, and fungi for more than 7 days byreleasing therapeutically effective amount of metal ions such as ionicsilver.

Yet another aspect of the present invention is to provide a suitablemethod of incorporating antimicrobial metallic compounds to effect moreuniform distribution of the said compound within the foam matrix duringthe process of making antimicrobial polyurethane foam.

The present invention also encompasses antimicrobial foams composed of:a flexible matrix of polyurethane material defining a plurality of opencells; and an antimicrobial metallic salt and/or antimicrobial metalnanoparticles uniformly distributed throughout the matrix. This foam maybe prepared utilizing the above-described processes and/or blends.

The present invention is further described by the examples which follow.Such examples, however, are not to be construed as limiting in any wayeither the spirit or the scope of the present invention.

EXAMPLES

All chemicals used in the examples described below were reagent gradeunless specified otherwise.

Example 1 Lab Scale Preparation of Antimicrobial Silver Foam

Samples of generally hydrophilic polyurethane foam in the form of squareslabs having approximate dimensions of about 10 inches×10 inches×1 inchin size and weighing approximately 150 grams each were preparedgenerally in accordance with the procedures set forth in PCTInternational Publication WO 2004/007595 A1 by Lendell et al. for“Antimicrobial Polyurethane Foam”.

The foam slabs were prepared so they would contain an antimicrobialactive agent in the form of silver at three target concentrations. Thesilver material elutes silver ions that provide antimicrobial activityand the concentrations of silver material generally correspond to thelevel of antimicrobial activity. These target concentrations were 500,1000, and 1500 ppm. The concentrations were achieved by adding eithersilver saccharinate powder or silver nanoparticles (or in some cases,both materials) to the ingredients used to make the polyurethane foam.The resulting foam slabs were tested for antimicrobial activity for 7days.

To make the foam slab, de-ionized water (˜180 ml), a compatiblesurfactant and a compatible polymeric thickener (each at a values lessthan 5% w/w), and the antimicrobial agent, either silver saccharinate orsilver nanoparticles or mixtures thereof, were mixed in a disposable waxpaper cup followed by a viscous polyurethane pre-polymer. The viscousmixture was quickly blended to uniformity using a high speed mixer (lessthan 1-2 minutes) and poured into a square shaped wax paper mold. Withinminutes, the contents poured into the mold expanded as the mixture beganto foam and cure. The mold was left undisturbed under very low lightinside a ventilated hood for about 30 minutes. At this time, the curedfoam mass was non-tacky to touch. The foam was removed from the mold andplaced on a stack of disposable paper towels and heated in microwaveoven for 5-10 minutes. The sample foam was then transferred to aconventional oven at 55° C. and thoroughly dried overnight. A controlfoam sample (Lendell Medisponge® 50P Hydrophilic Polyurethane Foam) wasmade the same way except the actives were left out.

The silver nanoparticles solution concentrate used in making the foamwas made following a procedure described in Example 93 of the U.S.Patent Application Publication No. US 2007/0207335 A1 “Methods andCompositions for Metal Nanoparticle Treated Surfaces” published Sep. 6,2007. The amount of each solution in the example was increased ten-fold.The combined solution but without any parts to be coated was heated to55° C. for 18 hours and cooled to room temperature. This solution wasdesignated in Table 1 below as “regular M8” solution. The regular M8solution was purified by a conventional dialysis method known to thoseordinarily skilled in the art to remove all inorganic and organic lowmolecular weight impurities and designated as “pure M8”.

The list of foam samples made, the active antimicrobial ingredient(s),and the amount of silver for each samples as calculated from theingredients and as determined by conventional flame atomic absorptionspectrophotometry (FAAS) techniques is presented in Table 1“Antimicrobial Silver Foam Samples, Silver Content, and ZOI (Zone ofInhibition) Assay Results”. As is evident from the results, there isconsiderable variability in the amount of antimicrobial silver observedfor the foam samples. It is generally believed this variability may bedue to the operator (but only for the samples that contain silvernanoparticles) and may be due to the non-uniform distribution of silversaccharinate particles (for those samples that contain silversaccharinate particles). The variability in the amount of silver in thesamples is believed to also be reflected in different durations ofsustained antimicrobial activity seen for the samples tested.

The antimicrobial efficacy of sample foams was tested against threerepresentative microorganisms (gram positive, gram negative, and afungus) which are identified as PSAE (Pseudomonas aeruginosa), Candida(Candida albicans) and MRSA (Methicillin-resistant Staphylococcusaureus). The data revealed none of the samples with 500 ppm Ag had muchactivity; the samples at 1000 ppm Ag had intermediate level activity andthose at 1500 ppm had the most activity regardless of the form ofsilver—saccharinate salt, nanoparticles, or a mix of the two. Theresults of this experiment led the inventors to conclude that 1500 ppmof Ag was likely to sustain the desired level of release of ionic silver(for lethal antimicrobial activity) for at least 5 days. For the samplesof silver-containing foam described in Example 2 below, a nominal targetof 1500 ppm of silver in the foam (on dry weight basis) was established.

TABLE 1 Antimicrobial Silver Foam Samples, Silver Content and ZOI AssayResults Sample ppm Ag ppm Ag PSAE Candida MRSA Sample # Type Theor.Meas. Last Day of Observed Zone 3 Regular M8 500 690 ± 62 None 1/2 Day 5None 4 Regular M8 1000 1438 ± 129 None None None 5 Regular M8 1500 2378± 145 2/2 Day 2 1/2 Day 7 None 6 AgSacc 500 129 ± 23 None 2/2 Day 1 None7 AgSacc 1000  803 ± 129 1/2 Day 2 2/2 Day 5 None 8 AgSacc 1500 1187 ±219 2/2 Day 5 1/2 Day 5 None 9 AgSacc 500  387 ± 117 None 1/2 Day 2 None(Lot 2) 10 AgSacc 1000 852 ± 44 1/2 Day 5 1/2 Day 6 None (Lot 2) 11AgSacc 1500 1395 ± 92  2/2 Day 7 2/2 Day 5 None (Lot 2) 12 Pure M8 500512 ± 50 None None None 13 Pure M8 1000  301 ± 373 1/2 Day 2 1/2 Day 5Outer side of foam down 0.5 mm ZOI 14 Pure M8 1500 1685 ± 47  1/2 Day 3None None 15 Pure 167 + 333 596 ± 11 None 1/2 Day 2 None M8 + AgSacc 16Pure 500 + 500 895 ± 41 1/2 zone 2/2 Day 5 None M8 + AgSacc Day 5 Outerside of foam down 17 Pure  500 + 1000 1654 ± 105 2/2 Day 7 202 Day 5None M8 + AgSacc 18 Reg. 167 + 333 Not None 1/2 Day 4 None M8 + AgSaccmeas. Note: M8 is the ID for silver nanoparticles concentrate solution;AgSacc stands for silver saccharinate.

Example 2 Large Scale Preparation of Antimicrobial Silver Foam

After setting a theoretical target of 1500 ppm Ag for large scaleproduction of polyurethane foam on the web in the form of rolls of foamsheet, machine trials were carried out on large scale foam manufacturingequipment, the details and operation of which are well known to those ofskill in the art. Another objective of the trials was to demonstratethat antimicrobial silver foam process was scalable (100 pounds orhigher lot size on dry foam basis). The pertinent details of machinetrials and the resulting data are presented in Table 2 “ProductionTrials of Antimicrobial Silver Foam” below.

TABLE 2 Production Trials of Antimicrobial Silver Foam Foam MeasuredTrial character- Ag (ppm) No. Target Ag (ppm) Foam size istics Note (2)1 1500 (1333 ppm ⅛″ and 3/16″ Golden yellow, ~400 ppm as AgSacc* thickand 13″-15″ pliable and & 167 ppm as wide in rolls stretchable, AgNP**)open cell (Note (1)) 2 1500 (1333 ppm ⅛″ and 3/16″ Golden yellow, ~860ppm as AgSacc thick and 13″-15″ pliable and & 167 ppm as wide in rollsstretchable, AgNP open cell 3 1500 (1333 ppm ⅛″ and 3/16″ Golden yellow,~960 ppm as AgSacc thick and 13″-15″ pliable and & 167 ppm wide in rollsstretchable, AgNP) open cell Note: (1) *AgSacc = Silver saccharinate;**AgNP = Silver nanoparticles concentrate; Note: (2) Silver in the foamanalyzed by FAAS

Three trials were attempted. Each successive trial was designed toinclude lessons learned from the previous trial. It was observed thatthe silver content of the foam from Trial #1 was much lower than thetarget value. After analyzing the test results, the conclusion wasreached that the cause of lower silver content of the foam was not dueto error in the FAAS analysis, but some deviation in the large scaleproduction process. Despite adding the correct amount of silver inaqueous solution in the feed tank, it somehow was not gettingincorporated into the foam. An observation was made that silversaccharinate particles were settling out of the aqueous solution andcollecting at the mixing tank bottom during a 30 minute period when theaqueous solution was not stirred. This 30 minute stoppage of the stirrerwas required by the process equipment and could not be avoided.

Before carrying out Trial #2, a test was carried out to examine theextent of silver saccharinate settling by sampling the suspension ofsilver-containing ingredients over 30 minutes at fixed time intervals of10 minutes after stirring was stopped. The sample aliquots were analyzedfor silver and revealed they contained an average 1277 ppm Ag (0 minutesafter stopping), 1126 ppm Ag (10 min), 1087 ppm Ag (20 min) and 1051 ppmAg (30 min). The decreasing trend in the data was apparent (i.e. thesilver saccharinate particles were settling out). Thus, a need to keepthe particulate suspension stirred during the foam production wasidentified and changes to the production procedure were made. The Trial#2 was performed with the modified procedure. The resulting foam sampleswere analyzed for silver and still showed silver content much less (860ppm) than the target value (1500 ppm Ag). Repeat analysis to account forall of the silver added to the aqueous solution indicated that while auniform suspension may have been present in the tank, the silversaccharinate may have slowly settled out in the piping and may have beentrapped on the in line filter used to keep dirt particles out.

The Trial #3 was designed to improve the outcome (i.e. increase theamount of silver in the finished foam product). One change made was toincrease the viscosity of the aqueous solution that included the silverparticles because it is well known that higher viscosity would increasethe drag force on suspended particles and thus decrease their settlingvelocity. This in turn would increase settling time and keep more solidssuspended. The viscosity of the aqueous solution was increased bydoubling the amount of thickener polymer and Trial #3 was repeated asbefore. The silver analysis of the finished foam material still was muchless than its target value (960 ppm vs. 1500 ppm). Collectively, theresults of the 3 trials revealed the stirring of aqueous solution as itwas fed to the web and increasing solution viscosity were not suitableapproaches to meet the need for a robust solution for predictable silverfoam target loading. For successful scale up of process for makingantimicrobial silver foam, a robust solution was needed.

Example 3 Preparation of Antimicrobial Foam Using Silver SaccharinAmmonia Complex

In the samples made in the previous two examples, silver saccharinatewas dispersed in polyurethane foam in the form of fine particles. Theresults of the foam production trial revealed that the amount of silverin the foam could not be reliably controlled in the current process bymodifying the process parameters such as stirring speed and viscosity.In order to overcome the settling of silver saccharinate particles, thesilver saccharinate was dissolved in aqueous ammonium hydroxide solutionto form soluble silver saccharinate ammonia complex. The complexsolution with added thickener and surfactant was used to produce thepolyurethane foam in accordance with the following general procedure.The surfactant and thickener are of the type known to those of skill inthe art.

About 180 g of de-ionized water was transferred to a large disposablepaper cup. To a 100 ml glass beaker, an amount of silver saccharinatewet cake to yield ˜1333 ppm in the resulting foam (based on the dryweight of the foam) was added, followed by 20 g of de-ionized water anda few drops of surfactant known to those of skill in the art of makingpolyurethane foam. The contents in beaker were gently stirred for 15minutes to re-suspend the solids and break up any chunks. Ammoniasolution (9%) corresponding to an ammonia to silver molar ratio of 3 wasadded slowly to the silver saccharinate suspension until all the solidswere dissolved. The pH of this solution was ˜11.0. To the water in apaper cup, surfactant (˜0.3% w/w), thickener (˜0.25% w/v), and asufficient amount of silver nanoparticles concentrate to yield ˜167 ppmin the resulting foam (based on the dry weight of the foam) were addedunder stirring to give an amber brown viscous solution.

The dilute silver saccharinate ammonia complex solution (in the glassbeaker) was added to the viscous solution (in the cup) and mixed in touniformity. A small amount of glacial acetic acid (about ¼ of the molesof ammonia added) was mixed to lower the pH from 11.0 back to a pH ofapproximately 9.0. Finally 150 g of polyurethane pre-polymer were addedto the aqueous mixture under vigorous stirring and poured into a 10inch×10 inch square wax paper mold. After 15 minutes, the non-tacky andwet foam was removed from the mold and dried in a conventionallaboratory microwave oven by repeatedly heating and cooling for a fewminutes, and repeating the cycle numerous times. The golden yellowcolored slab of foam about 1 to 2 inches thick was obtained.

Three samples from different parts of the foam slab were cut andanalyzed for silver by FAAS techniques. For silver analysis by FAAS, thefoam sample was digested in a mixture of 30% HNO₃ and 30% H₂O₂ overnightto obtain a low viscosity brown liquid. After additional dilution, thesample was analyzed by flame atomic absorption on a VARIAN 220S atomicabsorption spectrometer (available from Varian Inc., which is now partof Agilent Technologies, Inc., Santa Clara, Calif.) that was calibratedusing a set of known silver solution standards. The amounts of silver inthe tree foam samples were 1256, 1276 and 1306 ppm respectively. Thesevalues are quite close to the theoretical target value of 1500 ppmindicating that the use of silver saccharinate ammonia complex (a watersoluble form) was a better solution to solve the particulate suspensionproblem causing non-uniformity of silver in the foam matrix. Thisapproach not only eliminated the particulate suspension once and for allbut also provided a robust method for producing antimicrobial silverfoam with pre-determined silver loadings.

Example 4 Measurement of Properties and Broad Spectrum Anti-MicrobialActivity of Foam Made Utilizing Silver Saccharinate—Ammonia ComplexMethod

Polyurethane foam slabs (˜10″×10″×1″) were made generally in accordancewith the procedure outlined in Example 3. These foam slabs were preparedso they had silver contents of approximately 2500 ppm (Lot L11202008B)and approximately 4000 ppm (Lot 01292009), respectively. The samples cutfrom these slabs were used to assess the antimicrobial activity and todetermine physical properties (density, water absorption etc).

Results of Antimicrobial Testing

Antimicrobial activity of the polyurethane foams was evaluated againstclinical isolates of commonly implicated micro-organisms (gram positive,gram negative, and fungi) in infections for efficacy and durability. Thetesting was carried out as described in the specification section. Acommercially available antimicrobial foam product incorporating a silverantimicrobial material was used as a control sample. The commerciallyavailable antimicrobial foam product is available under the trade nameOptifoam® Ag from Medline Industries, Inc. of Mundelein, Ill.

Efficacy test results are tabulated in the Table 3 “AntimicrobialActivity of Antimicrobial Silver Foam (Lot # L11202008B) Against 6×1Clinical Isolates” and Table 4 “Antifungal Activity of Silver Foam (Lot# L11202008B) Against 2 Fungal Isolates” below. More than 99.99%reduction in bacterial count against all six isolates and greater than99% reduction against two fungal isolates was seen despite very highinitial inoculum levels (˜1e⁶ cfu/ml). The efficacy shown by theantimicrobial silver foam prototypes of the present invention match thatof the commercial Optifoam® Ag. In the case of Enterobacter cloacae itactually performed better. Against fungi, the prototypes were slightlybetter than Optifoam® Ag. Thus, the antimicrobial foam of the presentinvention exhibited broad spectrum antimicrobial activity againstbacteria and fungi.

The results of the durability testing are presented in Table 5“Antimicrobial Efficacy of Antimicrobial Silver Foam Against PseudomonasAeruginosa (Lot # L11202008B)” and Table 6 “Antimicrobial Efficacy ofAntimicrobial Silver Foam Against Staphylococcus aureus (MRSA) (Lot #L11202008B)”. The test was carried out against one representative straineach of gram positive (Staphylococcus aureus MRSA) and gram negativebacteria (Pseudomonas aeruginosa) recovered from clinical settings. Theduration of the test was 10 days at the end of which the samples wereexamined for antimicrobial efficacy.

The test data are considered remarkable in that the foam prototype after7 days showed a 99.99+% reduction against Pseudomonas aeruginosa andMRSA strains. The same activity level was maintained through 10 daysagainst Pseudomonas but it dropped slightly to 99% against MRSA after 7days through 10 days. In contrast, Optifoam® Ag exhibited 99.99%activity against Pseudomonas for 2 days and for one day against MRSA.Against MRSA, the inventive prototype foam performed consistently betterthan Optifoam® Ag.

The durability test results are extraordinary considering that Optifoam®Ag contains nearly 2.5 times more silver than 2500 ppm value in the foamsample tested.

A reasonable shelf life is expected for any antimicrobial silver foamproduct. Over that period, it must be storage stable and retain itsrequired function. To assess that the foam prototypes made did notdegrade in performance over time, there were tests of the antimicrobialproperty of freshly made sample foam and of the same sample foam after180 days in real time. The results are listed in Table 7 “AntimicrobialActivity of Silver Foam (Lot # L01292009) Against Two Clinical IsolatesAfter 180 Days”. As can be seen, the foam maintained 99.99% reductionefficacy even after 180 days, giving confidence that a 2 year shelf lifefor the inventive foam product is possible.

TABLE 3 Antimicrobial Activity of Antimicrobial Silver Foam (Lot #L11202008B) Against 6 X 1 Clinical Isolates **Average Log growth**Average Average Average Percentage in Log *Log reduction Reduction Logof Optifoam ®- growth in Optifoam ®- Optifoam ®- the Initial Ag AMsilver Ag AM silver Ag AM silver Clinical isolate Inoculum (+ve ontrol)PU foam (+ve ontrol) PU foam (+ve ontrol) PU foam Pseudomonas 5.99 1.001.00 4.99 4.99 99.9989 99.998 aeruginosa Staphylococcus 5.81 1.00 1.004.81 4.81 99.9984 99.9984 epidermidis Staphylococcus 6.26 2.28 1.00 3.985.26 99.9894 99.9994 aureus (MRSA) Enterobacter 5.88 5.12 1.00 0.76 4.8882.6815 99.9986 cloacae Enterococcus 6.00 1.00 1.00 5.00 5.00 99.999099.9990 faecalis (VRE) Escherichia coli 6.15 1.00 1.00 5.15 5.15 99.999299.9992

TABLE 4 Antifungal Activity of Silver Foam (Lot # L11202008B) Against 2Fungal Isolates **Average Log growth **Average Average AveragePercentage in Log *Log reduction Reduction Log of Optifoam ®- growth inOptifoam ®- Optifoam ®- the Initial Ag silver PU Ag silver PU Ag silverPU Clinical isolate Inoculum (+ve ontrol) foam (+ve ontrol) foam (+veontrol) foam Candida 5.48 3.66 3.18 1.81 2.30 98.4675 99.4983 albicansRhodotorula 5.00 3.07 2.95 1.93 2.06 98.8267 99.1212 glutinis

TABLE 5 Antimicrobial Efficacy Of Antimicrobial Silver Foam AgainstPseudomonas Aeruginosa (Lot # L11202008B) **Average **Average Log growthLog growth Average Log of in Opti- in AcryMed *Log reduction Initialfoam ®- Ag Antimicro- Opti- Antimicro- Test Inocu- (+ve bial silverfoam ®- bial silver points lum control) PU foam Ag PU foam Day 1 5.541.00 1.00 4.54 4.54 Day 2 5.84 1.00 1.00 4.84 4.84 Day 3 5.49 2.84 1.002.65 4.49 Day 4 5.62 4.88 1.00 0.74 4.62 Day 5 6.00 5.61 1.00 0.39 5.00Day 6 5.98 5.74 1.00 0.25 4.98 Day 7 6.02 6.00 1.00 0.02 5.02 Day 8 5.805.80 1.00 0 4.80 Day 10 5.44 1.00 1.00 4.44 4.44

TABLE 6 Antimicrobial Efficacy of Antimicrobial Silver Foam AgainstStaphylococcus aureus (MRSA) (Lot # L11202008B) **Average **Average Loggrowth Log growth Average Log of in Opti- in AcryMed *Log reductionInitial foam ®- Ag Antimicro- Opti- Antimicro- Test Inocu- (+ve bialsilver foam ®- bial silver points lum control) PU foam Ag PU foam Day 15.78 1.00 1.00 4.78 4.78 Day 2 5.91 2.71 1.00 3.20 4.91 Day 3 5.80 2.281.00 3.52 4.80 Day 4 6.31 2.28 1.00 4.03 5.31 Day 5 6.08 2.90 1.00 3.185.08 Day 6 6.04 3.07 1.00 2.97 5.04 Day 7 6.18 3.33 1.00 2.84 5.18 Day 86.14 4.14 3.14 2.00 3.00 Day 10 6.19 5.22 3.59 0.97 2.60

TABLE 7 Antimicrobial Activity of Silver Foam (Lot # L01292009) AgainstTwo Clinical Isolates After 180 Days **Average Log growth **AverageAverage Average Percentage in Log *Log reduction Reduction Log ofOptifoam ®- growth in Optifoam ®- Optifoam ®- the Initial Ag AM silverAg AM silver Ag AM silver Clinical isolate Inoculum (+ve ntrol) PU foam(+ve ontrol) PU foam (+ve ontrol) PU foam Pseudomonas 6.20 4.89 1.001.31 5.20 95.1403 99.9993 aeruginosa Staphylococcus 6.15 1.00 1.00 5.155.15 99.9992 99.9992 aureus (MRSA) *Log reduction: (Log of initialinoculum) − (Log survivors in the silver foam samples). Values representthe log reduction in duplicate assays at each test point. **Average Logvalues of 1.00 are reported indicating that counts between 1-25 cfu/mlfor a particular dilution is considered insignificant. A statisticallysignificant bacterial count is said to be in the range of 25-250 CFU/mlat a particular dilution.

Physical Property Measurements

Most pertinent physical properties of antimicrobial foam samples such aswater or saline uptake, the foam density, color, and the effect ofsterilization (electron-beam irradiation and ethylene oxide) weremeasured. Water or saline absorbency is important as the foam materialis often used to absorb exudate in wound care products. Thus sufficientabsorbency is essential to prevent leaks. In water absorbency orhydration test of the foam, a sample piece was weighed before and aftersoaking in water or saline for 1 hour at normal room temperature(approximately 25° C.). From the change in weight, the foam absorbencyor hydration was calculated as % based on its original weight as gramsof water or saline/grams of dry foam.

TABLE 8 Hydration of Silver Foam After 6 Months Lot L01292009 (n = 3)Time (days) % Hydration St dev 0 1229.8 51.01 180 1115.2 124.94

The results in Table 8 “Hydration of Silver Foam After 6 Months LotL01292009 (n=3)” show the antimicrobial foam is a good absorbentmaterial, absorbing nearly ˜12 times it weight in moisture. Itsabsorbency is not affected over time and is comparable for foams withand without silver present as well as with Optifoam® Ag (˜11.5 g water/gfoam).

Foam Density

This property is a measure of the porosity of the foam and related tothe average size of the cell in the open cell foam matrix. To determinefoam density, the dimensions in the x, y, and z directions of known foamsample were measured to calculate the foam volume. From its weight andvolume, the density was calculated in gm/cm³. The results are presentedin Table 9 “Foam Density Measurement Results”. The foam material of thepresent invention was a sample from Trial #3, Example 2. The resultsindicate that the inventive foam material is almost 60% less dense thanOptifoam® Ag. Visual examination of the two suggests that open cells inthe prototype foam are larger than those in Optifoam® Ag.

TABLE 9 Foam Density Measurement Results Foam Volume Mass ρ Avg. ρ IDType (cm³) (g) (g/cm³) (g/cm³) StDev 0121- Optifoam ® 2.5806 0.50760.1967 0.1940 0.0028 02A1 Ag 0121- 2.5806 0.5010 0.1941 02A2 0121-2.5806 0.4931 0.1911 02A3 0121- Ag Foam, 1.8589 0.1482 0.0797 0.07820.0020 02B1 ⅛″ Trial 0121- 3, 1.9219 0.1460 0.0760 02B2 Example 2 0121-2.0164 0.1593 0.0790 02B3

Foam Color

Over its suggested shelf life, the golden yellow color of the foamshould remain essentially unchanged. This is especially true for silvercontaining medical products as they often undergo discoloration overtime even if they are stored in light impervious packages. A change incolor could indicate loss of activity to a customer discouraging itsuse. The color of the foam material was quantified by measuring L, a*,b* co-ordinates at the start and after 180 days. During this period thesample was left undisturbed in a lab drawer. The L, a*, b* co-ordinatesof the test foam sample are listed in Table 10 “Average L, a*, b* ColorCo-Ordinates of Silver Foam (Lot # L01292009)”. The difference in L, a*,b* values is minimal indicating that the sample essentially did notexperience color change even after 180 days indicating good resistanceto color change when kept protected from light.

TABLE 10 Average L, a*, b* Color Co-Ordinates of Silver Foam (Lot #L01292009) Time (days) Foam Lot L a* b* 0 L01292009 71.34 3.41 40.23 (n= 3) 180 same 74.02 3.48 41.07 (n = 3)

Example 5 Scaled Production of Antimicrobial Silver Foam Using SilverSaccharinate-Ammonia Complex

After successfully producing antimicrobial silver foam using silversaccharinate-ammonia complex on small scale (slabs) and showingimprovement in the uniform retention of silver in the foam (measuredvalue of silver was within 15% of the target value; see Example 3above), scaled up production of the silver foam was attempted onconventional polyurethane foam manufacturing equipment (i.e. machinetrial). Because of the use of a water soluble form of silversaccharinate in the form of its ammonia complex, the problem associatedwith poor suspension of insoluble silver saccharinate particles waseliminated. Thus, during the machine trial all equipment and processsteps were operated as if there was no suspended material in the aqueoussolution. However, the aqueous solution was stirred for a longer periodthan before (2 hours vs. 15 minutes) to ensure all insoluble silversaccharinate was converted to its soluble ammonia complex before thefoaming step was begun.

Additionally, changes were made to the web speed and temperaturesettings of the curing and drying sections of the oven through which theweb traveled. These changes ensured the foam exiting the oven was tackfree and had the right amount of moisture. Following its exit, the foamwas cooled to room temperature as it passed over a set of rollers andwas rolled onto spools. Three rolls were made (front, middle and back)and each spool roughly held 100 ft. of foam.

Analysis of Foam Sheet Material

The foam sheet material from each roll was analyzed for silver. Thesilver values (average (n=3) ˜3550 ppm) were found to be within 12% ofthe target value of 4000 ppm. This was considered a remarkableimprovement over the results of earlier trials employing silversaccharinate particulate suspension to make the foam. The actual silvercontent of the foam from those trials averaged 36-43% less than thetarget value of 1500 ppm. Clearly, the approach of converting insolublesilver saccharinate to its soluble ammonia complex permitted a morerobust process and thus produced foam whose silver content was closer toits target.

The finished foam sheet material did not emit any ammonia odor due toany residual silver salt ammonia complex form indicating that all ofammonia complex had reverted back to silver saccharinate. Further,de-ionized water (˜50 ml) in which the foam sheet samples (˜1 g weight)were immersed and repeatedly underwent several absorption and squeezecycles at 25° C. did not register alkaline pH (due to residual ammonia).

In a recent zone-of-inhibition (ZOI) assay, a foam sheet sampleexhibited large zones of inhibition against Pseudomonas aeruginosa andMRSA after nearly 18 months in storage at room temperature protectedfrom light. This clearly demonstrated excellent storage stability of theantimicrobial foam sheet material made in this example.

Example 6 Effect of Sterilization by ETO and E-Beam on the AntimicrobialSilver Foam

For the antimicrobial silver foam of the present invention to havecommercial utility, it is important that it withstands conventionalethylene oxide (ETO) sterilization methods and conventional electronbeam (E-beam) irradiation sterilization methods that are common inmedical device industry. For example, any adverse effect such as drasticcolor or shade change post sterilization would not only affect itsappearance (silver containing matrices tend to discolor or darken) butmay affect its efficacy as well.

One inch wide and ˜10″ long strips of antimicrobial silver foam (Sample#4, #11, and #17 from Example 1) were sealed in ETO and E-beamcompatible packages and sent out for sterilization at commercialsterilization facilities. Standard commercial ETO process and E-beam at˜25 kGy were carried out. The samples were returned and examined forappearance. No difference in color was observed between non-sterilizedand sterilized samples.

More particularly, FIG. 1 is a black and white photograph illustratingsamples of antimicrobial polyurethane foam containing silvernanoparticles (Sample #4, Example 1) after sterilization by electronbeam irradiation and ethylene oxide techniques and a control sample.FIG. 2 is a black and white photograph illustrating samples ofantimicrobial polyurethane foam containing silver saccharinate (Sample#11, Example 1) after sterilization by electron beam irradiation andethylene oxide techniques and a control sample. FIG. 3 is a black andwhite photograph illustrating samples of antimicrobial polyurethane foamcontaining both silver nanoparticles and silver saccharinate (Sample#17, Example 1) after sterilization by electron beam irradiation andethylene oxide techniques and a control sample. As is evident from theblack and white photographs, no significant difference in shade wasobserved between the control samples and the sterilized samples.Additionally, during inspection of the samples, no difference in colorwas observed between the control samples and the sterilized samples.

While the present invention has been described in connection withcertain preferred embodiments it is to be understood that the subjectmatter encompassed by way of the present invention is not to be limitedto those specific embodiments. On the contrary, it is intended for thesubject matter of the invention to include all alternatives,modifications and equivalents as can be included within the spirit andscope of the following claims.

We claim:
 1. An antimicrobial polyurethane foam comprising a reactionproduct of: a multi-functional isocyanate component; an aqueous polyolcomponent reactive with the multi-functional isocyanate component; anantimicrobial metallic compound; and a complexing agent, wherein theantimicrobial metallic compound and the complexing agent form a complex,wherein the complex is adapted to allow dissipation of the complexingagent such that the antimicrobial metallic compound is present assubstantially the only antimicrobial metallic compound in theantimicrobial polyurethane foam, wherein the complexing agent isselected from amine compounds, ammonium-containing compounds andammonia, further wherein the polyurethane foam comprises a flexiblematrix of polyurethane material defining a plurality of open cells,wherein the antimicrobial metallic compound is uniformly distributedthroughout the flexible matrix.
 2. The antimicrobial polyurethane foamof claim 1, wherein the antimicrobial metallic compound is a silver,zinc or copper compound.
 3. The antimicrobial polyurethane foam of claim1, wherein the aqueous polyol component is selected frompolyhydroxy-containing polyesters, polyoxyalkylene polyether polyols,polyhydroxyterminated polyurethane polymers, polyhydroxy-containingphosphorus compounds, and alkylene oxide adducts of polyhydricpolythioesters, polyacetals, aliphatic polyols and thiols, and mixturesthereof.
 4. The antimicrobial polyurethane foam of claim 1, wherein themulti-functional isocyanate component is selected from the groupconsisting of toluene diisocyanate, monomeric methylene diisocyanate,polymeric methylene diisocyanate, and combinations thereof.
 5. Theantimicrobial polyurethane foam of claim 2, wherein the antimicrobialmetallic compound is selected from silver diazepine complexes, polymericsilver compounds, and silver compounds of saccharin.
 6. Theantimicrobial polyurethane foam of claim 5, wherein the antimicrobialmetallic compound is selected from silver saccharinate.
 7. Theantimicrobial polyurethane foam of claim 1, further comprising a chainextender.
 8. The antimicrobial polyurethane foam of claim 3, wherein theaqueous polyol component is a polyether polyol.